BRAVOO study
Better understanding of reactive arthritis in children to prevent overtreatment and unnecessary consumption of care

Immune-mediated or reactive arthritis is the most common form of arthritis in
children. In this case, inflammation in the joint is caused by an ongoing
immune response following a bacterial or viral infection elsewhere in the body.
This is a mild form of arthritis that is treated with non-steroidal
anti-inflammatory drugs (NSAID*s) and occasionally with intra-articular
injections with corticosteroids. Less common are the other two most common
types of arthritis in children: bacterial arthritis that requires a hospital
stay and rapid intravenous antibiotics to prevent severe joint damage and
Juvenile Idiopathic Arthritis (JIA). JIA is diagnosed if the arthritis is
present for more than six weeks and no other (microbial) causes have been
identified. The children with JIA are referred to an academic center where
long-term treatment and follow-up take place. The problem is that we are
currently unable to properly distinguish these three types of arthritis, mainly
because reactive arthritis is not well recognized with current diagnostic
tests.

The aim of this study is to determine the known and unknown pathogens of
reactive arthritis in children between six months to 18 years old. We will use
a protocolized approach of diagnostic testing in order to develop an evidence
based clinical diagnostic guideline. By identifying pathogens leading to
reactive arthritis and excluding bacterial arthritis and JIA, reactive
arthritis can be diagnosed in an early stage followed by adequate treatment.

Multicenter prospective observational study.

As part of routine clinical care, the following diagnostics will be carried out:

- Blood test on day 0, and optionally on day 14 and day 28-42.
- Nasopharyngeal swabs.
- Throat culture.
- Stool test.
- Synovial fluid analysis (only on indication).
- Radiology: conventional X-ray of the affected joint and, if indicated,
ultrasound of the affected joint / MRI of the affected joint.

The following study procedures will take place:
- Extra blood or synovial fluid when blood or synovial fluid is collected as
part of routine clinical care. Blood will be taken up to 3 times for the study
over a six-week period. The blood sampling will remain within the limits of the
WHO guidelines on peripheral blood sampling for minors of 2015 (~0,8
ml/kg/sampling time with a maximum of 50 ml/draw, not exceeding six times a
year).
- Nasopharyngeal swabs will be taken during outpatient visits (maximum three
times).
- Patients will complete a short questionnaire regarding quality of life at the
first visit, at six weeks and at 12 weeks after diagnosis.

With these study procedures, we estimate the burden and risk to the patient as
minimal.